"I've missed way too much for way too long.and I'm done", he said in the post.
Harrison played almost his entire career with the Steelers and the 84.5 sacks he collected while wearing black-and-gold are a franchise record.
The Ohio native ends his career as a two-time Super Bowl champion and a five-time Pro Bowler.
Harrison signed a one-year contract with the New England Patriots at the end of 2017 and played in Super Bowl LII.
Having gone undrafted in 2002, he eventually joined the Pittsburgh roster in 2004 where he won the Super Bowl in 2006 and 2009, where he famously scored an 100-yard interception touchdown against the Atlanta Falcons.
He added the hashtag #2ndAndFinalRetirment to the post in reference to his brief retirement in August 2014 before returning to the Steelers the following month.
Longtime Pittsburgh Steelers linebacker James Harrison is taking a second crack at retirement.
This is the second time Harrison has called it quits. However, he had a change of heart and continued to play on for a few more seasons. He played sparingly for much of 2017 and the Steelers granted him his release in December.
He played 14 of his 15 National Football League seasons with the Steelers, twice earning first-team All-Pro honours and being named to the Pro Bowl five times in consecutive seasons from 2007-11.